Step 1) Calibrate space and time (standardize on cell cycle model)

Pick a fixed duration cell cycle. Check for growth anisotropy.

Typical cell division parameters:

Graphs:
Step 2) Cell division with contact inhibition

A standard sigmoid function of growth rate (rate of increase of target area) versus the ratio of cell perimeter in contact with medium and total perimeter of cell. When ratio is 0, cell is completely surrounded with some base growth rate. When ratio is 1, cell is completely isolated and it can reach its target area with maximum growth rate.

Graphs:
Step 3) External force calibration

Once space and time are calibrated, external force can be calibrated in non-inertial motion of cells. We can define a unit of external force as the amount of model specific force required to move a cell with center of mass at (0 μm, 0 μm) to (5 μm, 0 μm).

Step 4) Cell-cell and cell-ECM adhesion

This is a new term in the Hamiltonian/potential energy for some models. Ensure that the overall adhesion energy does not dominate. How much pulling force is required to separate cells?

Step 5) A comparative study

Examples: cell sorting, tissue invasion, wound healing assay, tissue folding, collective migration, rosette formation, etc.

Research Questions:

If a single cell is allowed to grow in a confined space (with periodic boundary conditions), what is the maximum number of cells that can be accommodated?

Does the rate of cell sorting and wound healing depend on choice on model?

Does greater flexibility in cell shape representation lead to more realistic tissue folding/invagination?

Can rosette formation be achieved using only cell polarity and external forces?
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